AB0098 THE CAUSAL RELATIONSHIP BETWEEN MULTIPLE SCLEROSIS AND PSORIASIS: A TWO-SAMPLE MENDELIAN RANDOMIZED STUDY
Authors: Y. Xu, Z. Duan, J. Wang, S. Song, J. Qiao, S. X. Zhang, X. Li
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriasis is an immune-related, chronic inflammatory skin disease.The disease often presents with clearly delineated areas of erythematous patches on the skin covered with silvery scales<sup>[1]</sup>.As the research progresses, more and more evidence suggests that multiple sclerosis may help reduce the occurrence of psoriasis. <h3>Objectives</h3> To explore whether there is a causal relationship between having multiple sclerosis and obtaining psoriasis. <h3>Methods</h3> We used a 2-sample Mendelian randomization (MR) method to evaluate the causal effect of multiple sclerosis on psoriasis. Multiple sclerosis (MS) and psoriasis (Ps) Ps summary data from IEU database (http://gwas.mrcieu.ac.uk/).The multiple sclerosis cohort consisted of 9,722 samples and 17,376 controls.The psoriasis cohort consisted of 4510 samples and 212242 controls.To reduce bias due to race-related confounding factors, the genetic background of the study population was limited to European ancestry.In the MR Approach, the IV analysis is based on three strict assumptions, namely that IV should be strongly correlated with exposure, independent of confounding factors associated with direction and outcome, and influence outcome solely through exposure<sup>[2]</sup>. We screened for significant (p&lt;5× 10-06) and approximately independent (r 2 &lt; 0.01) genome-wide single nucleotide polymorphisms (SNPS) and retained only SNPS with scores over 10 that were considered sufficiently strongly associated. To estimate the causal relationship between exposure and outcome, inverse variance weighting (IVW), MR-Egger regression, and weighted median methods were used. Mendelian random multivariate residuals and outliers, Cochran Q test and MR-Egger regression were used for sensitivity analysis. <h3>Results</h3> MR Statistics showed that genetic prediction of multiple sclerosis was associated with a reduced risk of psoriasis (IVW: OR=0.698,95%CI= 0.5788-0.843 P= 2.098-e-2), which we found to be statistically significant as the weighted median method (OR=0.827; 95%CI= 0.760- 0.898p =4.476e-06), MR-Egger also showed a similar effect (OR=0.668; 95%CI= 0.482-0.926 P = 2.184e-02). Cochran’s s Q test (Q=322.585; p=9.057e-51) found potential heterogeneity. MR-egger regression (P=0.164, intercept=0.043) was used to test the nonexistent horizontal multi-directivity. Similarly, we examined the level of pleiotropy again with MR-PRESSO’s global test, and the results showed no evidence of horizontal pleiotropy. In addition, no SNP was found to be a significant factor affecting the association in the residual analysis. <h3>Conclusion</h3> Our results provide causal evidence for the effect of multiple sclerosis on psoriasis risk. This Mendelian randomization study showed a causal relationship between multiple sclerosis and the risk of psoriasis. Multiple sclerosis may help reduce the burden of psoriasis. <h3>References</h3> [1]Li Y, Guo J, Cao Z, Wu J. Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study. Front Immunol. 2022 Jun 10;13:916645. doi: 10.3389/fimmu.2022.916645. PMID: 35757704; PMCID: PMC9226443. [2]Storm CS, Kia DA, Almramhi M, Wood NW. Using Mendelian randomization to understand and develop treatments for neurodegenerative disease. Brain Commun. 2020 Mar 20;2(1):fcaa031. doi: 10.1093/braincomms/fcaa031. PMID: 32954289; PMCID: PMC7425289. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.